Mice lacking macrophage 12/15-lipoxygenase are resistant to experimental hypertension

In mouse arteries, Alox15 [leukocyte-type 12/15-lipoxygenase (LO)] is assumed to regulate vascular function by metabolizing arachidonic acid (AA) to dilator eicosanoids that mediate the endothelium-dependent relaxations to AA and acetylcholine (ACh). We used Alox15(-/-) mice, made by targeted disruption of the Alox15 gene, to characterize its role in the regulation of blood pressure and vascular tone. Systolic blood pressures did not differ between wild-type (WT) and Alox15(-/-) mice between 8-12 wk of age, but Alox15(-/-) mice exhibited resistance toward both N(G)-nitro-L-arginine-methyl ester (L-NAME)- and deoxycorticosterone acetate (DOCA)/high-salt-induced hypertension. ACh relaxed mesenteric arteries and abdominal aortas of WT and Alox15(-/-) mice to an identical extent. The LO inhibitor nordihydroguaiaretic acid attenuated the ACh relaxations by 35% in arteries from both WT and Alox15(-/-) mice. Reverse-phase HPLC analysis of [(14)C]AA metabolites in aorta and peritoneal macrophages (PM) revealed differences. Unlike PM, aorta tissue did not produce detectable amounts of 15-hydroxyeicosatetraenoic acid. Although Alox15 mRNA was detected in aorta, high-resolution gel electrophoresis with immunodetection revealed no Alox15 protein expression. Unlike aorta, Alox15 protein was detected in PM, intestine, fat, lung, spleen, and skin from WT, but not Alox15(-/-), mice. Injection of WT PM, a primary source of Alox15 protein, into Alox15(-/-) mice abolished their resistance toward L-NAME-induced hypertension. On the other hand, WT mice acquired resistance to L-NAME-induced hypertension after depletion of macrophages by clodronate injection. These studies indicate that Alox15 is involved in development of experimental hypertension by altering macrophage functions but not via synthesis of the vasoactive LO metabolites in mouse arteries.     

Analysis of the conformation and function of the Plasmodium falciparum merozoite proteins MTRAP and PTRAMP

Thrombospondin repeat (TSR)-like domains are structures involved with cell adhesion. Plasmodium falciparum proteins containing TSR domains play crucial roles in parasite development. In particular, the preerythrocytic P. falciparum circumsporozoite protein is involved in hepatocyte invasion. The importance of these domains in two other malaria proteins, the merozoite-specific thrombospondin-related anonymous protein (MTRAP) and the thrombospondin-related apical membrane protein (PTRAMP), were assessed using near-full-length recombinant proteins composed of the extracellular domains produced in Escherichia coli. MTRAP is thought to be released from invasive organelles identified as micronemes during merozoite invasion to mediate motility and host cell invasion through an interaction with aldolase, an actin binding protein involved in the moving junction. PTRAMP function remains unknown. In this study, the conformation of recombinant MTRAP (rMTRAP) appeared to be a highly extended protein (2 nm by 33 nm, width by length, respectively), whereas rPTRAMP had a less extended structure. Using an erythrocyte binding assay, rMTRAP but not rPTRAMP bound human erythrocytes; rMTRAP binding was mediated through the TSR domain. MTRAP- and in general PTRAMP-specific antibodies failed to inhibit P. falciparum development in vitro. Altogether, MTRAP is a highly extended bifunctional protein that binds to an erythrocyte receptor and the merozoite motor.     

ABA says NO to UV-B: a universal response?

Abscisic acid (ABA) signaling pathways have been widely characterized in plants, whereas the function of ABA in animals is less well understood. However, recent advances show ABA production by a wide range of lower animals and higher mammals. This enables a new evaluation of ABA signaling pathways in different organisms in response to common environmental stress, such as ultraviolet (UV)-B. In this opinion article, we propose that the induction of common signaling components, such as ABA, nitric oxide (NO) and Ca(2+), in plant and animal cells in response to high doses of UV-B, suggests that the evolution of a general mechanism activated by UV-B is conserved in divergent multicellular organisms challenged by a changing common environment.     

Further studies on the antigonadotropic mechanism of action of norethisterone.

To examine the molecular mechanisms involved in the antigonadotropic effects of norethisterone (NET) and two of its A-ring reduced metabolites the 5 alpha-norethisterone (5 alpha-NET) and the 3 beta, 5 alpha-norethisterone (3 beta, 5 alpha-NET) at the neuroendocrine level, a series of experiments were undertaken in adult castrated rats. Animals were primed either with 0.2 mg of tamoxifen (Tam) for 4 consecutive days or 1.0 mg of cyproterone acetate (CPA) for 7 days followed by a single subcutaneous injection of 0.5 mg of NET, 5 alpha-NET or 3 beta, 5 alpha-NET. Four hours later, they were sacrificed and blood obtained for the measurement of immunoreactive serum LH and FSH. The results indicated that antiestrogen (Tam) pretreatment precluded the inhibitory effects of NET and the 3 beta, 5 alpha-NET but not those of the 5 alpha-NET derivative. Pretreatment with CPA did not modified the antigonadotropic action of the 3 beta, 5 alpha-NET metabolite but it markedly reduced the inhibitory action of the 5 alpha-NET, thus indicating that in the experimental model used, the antigonadotropic effects of NET, are in part the result of its metabolic conversion to its A-ring reduced metabolites. While the 5 alpha-NET displayed an androgenic effect, the 3 beta, 5 alpha-NET exhibited estrogen-like effect at the neuroendocrine level.     

Distal conformation of thyroid hormones. The crystal structure of 3,5,3'-triiodothyroacetic acid H-diethanolamine (1:1) complex

In the crystal structure of a complex of the hypocholesteremic thyromimetic agent, 3,5,3′-triiodothyroacetic acid and N-diethanolamine (1:1), the 3′-iodine is observed for the first time in the distal position, away from the α-ring of the diphenyl ether portion of a thyroactive analogue of thyroxine. This result was anticipated from stereochemical and biological activity studies. However, previous observations of structures in which the 3′-iodine was proximal had cast some doubt on the stability of the 3′-distal conformation. The present evidence now suggests that the relative energies of the two conformers are similar and that both conformers are readily accessible in solution.     

Structural Design Principles of Complex Bird Songs: A Network-Based Approach

Bird songs are acoustic communication signals primarily used in male-male aggression and in male-female attraction. These are often monotonous patterns composed of a few phrases, yet some birds have extremely complex songs with a large phrase repertoire, organized in non-random fashion with discernible patterns. Since structure is typically associated with function, the structures of complex bird songs provide important clues to the evolution of animal communication systems. Here we propose an efficient network-based approach to explore structural design principles of complex bird songs, in which the song networks–transition relationships among different phrases and the related structural measures–are employed. We demonstrate how this approach works with an example using California Thrasher songs, which are sequences of highly varied phrases delivered in succession over several minutes. These songs display two distinct features: a large phrase repertoire with a ‘small-world’ architecture, in which subsets of phrases are highly grouped and linked with a short average path length; and a balanced transition diversity amongst phrases, in which deterministic and non-deterministic transition patterns are moderately mixed. We explore the robustness of this approach with variations in sample size and the amount of noise. Our approach enables a more quantitative study of global and local structural properties of complex bird songs than has been possible to date.     

Geosphere-Biosphere Interactions in Bio-Activity Volcanic Lakes: Evidences from Hule and Rìo Cuarto (Costa Rica)

Hule and Río Cuarto are maar lakes located 11 and 18 km N of Poás volcano along a 27 km long fracture zone, in the Central Volcanic Range of Costa Rica. Both lakes are characterized by a stable thermic and chemical stratification and recently they were affected by fish killing events likely related to the uprising of deep anoxic waters to the surface caused by rollover phenomena. The vertical profiles of temperature, pH, redox potential, chemical and isotopic compositions of water and dissolved gases, as well as prokaryotic diversity estimated by DNA fingerprinting and massive 16S rRNA pyrosequencing along the water column of the two lakes, have highlighted that different bio-geochemical processes occur in these meromictic lakes. Although the two lakes host different bacterial and archaeal phylogenetic groups, water and gas chemistry in both lakes is controlled by the same prokaryotic functions, especially regarding the CO₂-CH₄ cycle. Addition of hydrothermal CO₂ through the bottom of the lakes plays a fundamental priming role in developing a stable water stratification and fuelling anoxic bacterial and archaeal populations. Methanogens and methane oxidizers as well as autotrophic and heterotrophic aerobic bacteria responsible of organic carbon recycling resulted to be stratified with depth and strictly related to the chemical-physical conditions and availability of free oxygen, affecting both the CO₂ and CH₄ chemical concentrations and their isotopic compositions along the water column. Hule and Río Cuarto lakes were demonstrated to contain a CO₂ (CH₄, N₂)-rich gas reservoir mainly controlled by the interactions occurring between geosphere and biosphere. Thus, we introduced the term of bio-activity volcanic lakes to distinguish these lakes, which have analogues worldwide (e.g. Kivu: D.R.C.-Rwanda; Albano, Monticchio and Averno: Italy; Pavin: France) from volcanic lakes only characterized by geogenic CO₂ reservoir such as Nyos and Monoun (Cameroon).     

Genomic and anatomical comparisons of skin support independent adaptation to life in water by cetaceans and hippos

1. Download : Download high-res image (111KB)
2. Download : Download full-size image